EP3723588B1 - Combined examination with imaging and a laser measurement - Google Patents

Description

The invention relates to a device that makes it possible to fuse large-area information from a sample obtained by imaging with locally queried information about certain properties of the sample.

State of the art

Imaging methods are often used to examine the properties of samples, such as biological tissue. In particular, optical images can be obtained very quickly, even from spatially extensive samples, such as an entire organ. For example, such an image can contain information about what portion of the spectrum offered by a light source is reflected by the sample.

Sometimes this information is not sufficient to provide a conclusive answer to the question posed at the beginning of the investigation. For example, an optical change in tissue can result from an illness, but it can also have another cause. A chemical examination, for example using molecule-specific Raman spectroscopy, can clarify whether, for example, tumor markers are present in the tissue.

However, such an investigation is difficult to carry out in vivo. Most Raman spectroscopy instruments are designed to analyze small samples on slides or in cuvettes large organ would first have to be removed. Examples of such devices are optical microscopes expanded with a Raman spectrometer. In principle, the laser beam could be directed at the organ from a greater distance. However, it is then difficult to collect enough of the Raman-scattered light emitted in all directions.

US 2012/123 205 A1 discloses a system with which an overview image of an operating area produced with visible light can be produced during an operation using, for example, an endoscopic probe, with information then being superimposed on this overview image, which is obtained by locally querying parts of the operating area with a laser beam emerging from the probe were recorded.

US 2017/160 201 A1 discloses a further examination device with which an extensive object can be examined, with an overview image produced with visible light and information queried locally with a laser beam being fused and synthesized.

US 2009/244 260 A1 discloses an endoscope system that creates a dot pattern in the examined area by spatially scanning and modulating the intensity of a laser beam and reconstructs three-dimensional shapes from an optical image of this dot pattern.

US 2007/161 906 A1 discloses a device to support dermatological procedures that optically detects blood vessels hidden in the skin and projects them onto the surface of the skin, for example to facilitate treatment of these blood vessels.

WO 2013/010 910 A1 discloses a method by which a 3D scan of a solid object, such as a tooth, is removed from interference caused by temporary im Moving objects in the field of vision, such as cheeks or a tongue, can be corrected.

Task and solution

It is therefore the object of the invention to provide a device with which a property can be queried locally with a laser beam on a spatially extended sample and this property can be used in the best possible way for spatially selective work on the sample in relation to the queried property, such as surgical ones Interventions can be made usable.

This object is achieved according to the invention by a device according to claim 1. Further advantageous refinements result from the subclaims related thereto.

Subject of the invention

As part of the invention, a device for examining a sample was developed. This device includes an imaging device for obtaining an overview image of the sample, such as a camera or an arrangement of cameras. The device further comprises a measuring instrument for locally querying at least one property of the sample with a laser beam which emerges from an aperture, tracking means for determining the location on the sample that is currently being queried with the laser beam, and a memory in which the Laser beam queried property is associated with the determined location on the sample.

According to the invention, said tracking means are designed to determine the location at which the laser beam hits the sample by evaluating the resulting laser point from the overview image, and/or to determine this location by measuring the position and orientation of the aperture.

It was recognized that in this way it becomes possible to get close to the sample with the aperture, even with a spatially extensive sample, such as a complete organ. The aperture can therefore cover a large part of the solid angle into which the sample emits light when interrogated by the laser beam. A large portion of this light can then be collected and used for evaluation.

This represents a paradigm shift compared to the microscopes in question, which are expanded to include Raman spectrometers. In these microscopes, the location on the sample that is examined with the laser beam is known in advance, since the sample is attached, for example, to a positioning table that is moved in a defined manner relative to the aperture. This means that it is in no way difficult to assign the property queried with the laser beam to a specific location on the sample. It was recognized that with spatially extensive samples it is technically difficult to move the aperture close to the sample from a great distance in a manner known in advance. Instead, it is advantageous to initially completely abandon the knowledge of which location on the sample is currently being queried with the laser beam and then determine it again later.

However, the concept of querying a property on the sample with the laser beam is not limited to the sample generating an optical signal in response to the laser beam and this being evaluated. For example, the sample can also be locally heated by the laser beam and this heating can be observed in the far field with a thermal imaging camera. Likewise, for example, locally Material is removed from the sample and sucked into a mass spectrometer to determine the chemical composition.

According to the invention, the aperture is part of a probe that can be manually guided to the sample by the operator of the device. While the aim is usually to automate and mechanize as many steps as possible, manual positioning of the aperture is particularly advantageous when examining tissue during an operation. Mechanized positioning with a robot arm would require considerable effort, and in particular it would have to be ensured that no injuries arise due to excessive force exerted by the robot arm. A lot of space would also be required for the robot arm, which is often not available in a surgical scenario. By carrying out the positioning manually and shifting the automation to the subsequent determination of the examined location on the sample, the strengths of the operator on the one hand and the technology on the other are optimally combined. This also enables the realization of a transportable unit that is not tied to a specific space.

The concept of manual control is not limited to the probe being held in the hand. Rather, this term also includes, for example, that the probe is guided through the working channel of an endoscope to an organ. In general, due to time constraints, the entire extended sample is not examined in detail with the laser beam, but rather specific locations are selected for this examination based on the overview image. The operator can use the quick hand-eye coordination and at the same time also use his sense of touch to avoid injuries caused by excessive force on tissue. The operator can therefore concentrate purely on the medical aspects of the examination, while the device takes care of that in the background Complexity takes care of combining the result of the detailed examination by the laser beam with the overview image.

The probe advantageously has a manually operable trigger for querying the property by the measuring instrument. Querying the property is not possible in real time for every type of examination. For example, recording a Raman spectrum can take a few seconds. This could result in having to wait for the current recording to end after positioning the probe at a point of interest. However, if the recording is started by pressing the shutter button, this waiting time is eliminated.

As the distance between the probe and the sample changes, the focal plane of the laser beam emerging from the aperture may also change. The extent to which this affects the interrogation of the properties of the sample with the laser beam depends on which physical contrast mechanism is used during the interrogation and how quickly this interrogation takes place. For example, recording a Raman spectrum can take a few seconds and can be "blurry" if there is too much relative movement between the probe and sample, similar to a photo that is taken with a correspondingly long exposure time. The relative movement can be caused, for example, by manual guidance of the probe, but also, for example, by the natural movement of the sample, which can be a living organ. Therefore, in a further particularly advantageous embodiment of the invention, tracking means are provided which are designed to track the focal plane of the laser beam emerging from the aperture to a change in the distance between the aperture and the sample.

These tracking means can, for example, be designed to automatically readjust the focal plane of the laser and/or the focal plane of the light coupling into an optical waveguide leading to the aperture. For this purpose can the distance between the probe and the sample can be determined in any way. For example, the probe can have a measuring device for the distance between the probe and the sample. This measuring device can, for example, have a transmitter for an electromagnetic wave and/or for ultrasound, as well as a receiver for the wave reflected by the sample or the ultrasound reflected by the sample. The distance between the aperture and the sample can also be determined, for example, using any image that shows both the probe and the sample. This image can be a camera image, for example, but can also be obtained in any other way, for example by evaluating terahertz radiation.

The refocusing can be carried out, for example, with the help of fast mechanical movement mechanisms, with the help of liquid lenses or with any other adaptive optics.

Tracking the focal plane also makes it possible, in particular, to keep the focal plane stable when the aperture is moved, for example manually, over an extensive area on the sample. This means that the measured values for the properties of the sample obtained at different locations on the sample become more comparable.

In a particularly advantageous embodiment of the invention, the tracking means include an image evaluation logic which is designed to detect a location at which the luminance of the overview image exceeds a threshold value, a center of gravity of the luminance of the overview image, and/or a location at which a spatial profile of the Luminance of the overview image matches the beam profile of the laser beam than identifying the location on the sample that is currently being queried with the laser beam. The laser light is much more directed than, for example, lamp light, which is used to create an optical overview image, and is therefore typically dominant in luminance. A secure identification of the The location that is currently being queried with the laser beam is also possible if parts of the sample have the same color as the laser beam.

In a further advantageous embodiment of the invention, a modulator is provided for modulating the intensity of the laser beam with a frequency ω. Furthermore, the device for obtaining the overview image is expanded in such a way that it can record a chronological sequence of overview images. The tracking means include an image evaluation logic that is designed to identify, from the temporal sequence of overview images, a location at which the luminance is modulated with the frequency ω as the location on the sample that is currently being queried with the laser beam. In this way, the location currently being queried can still be identified even if the laser intensity used is very low and the luminance caused by the laser beam lags behind the dominance caused by other light sources.

In a further particularly advantageous embodiment of the invention, the tracking means comprise at least two laser scanners or radio transmitters for spatial tracking of the aperture or the probe. These devices can, for example, be placed in the corners of an operating room where they do not disturb and track the position and orientation of the probe throughout the entire operating room.

In a further advantageous embodiment of the invention, the measuring instrument additionally comprises a scanning device which is designed to change the exit angle of the laser beam from the aperture. In this way, the point examination with the laser beam can be expanded to examine a limited area on the sample.

In a particularly advantageous embodiment of the invention, the measuring instrument contains a Raman spectrometer for querying the chemical composition of the sample. Each molecule leaves one in the Raman spectrum characteristic fingerprint, so that, for example, the composition of mixtures can be clearly determined. In particular, tumor tissue can be clearly identified via the presence of tumor markers. Furthermore, the Raman-scattered light from the sample can be separated from the laser beam used for the query by spectral filtering, since it is wavelength-shifted compared to the laser beam.

Any corrections can be applied to the Raman spectrum. For example, a fluorescent background can be separated by a fit using polynomials, EMSC or a least squares method.

In a particularly advantageous embodiment of the invention, an excitation laser on the one hand and the Raman spectrometer on the other hand are connected to a common optical fiber leading to the aperture via a fiber coupler, the division ratio of which is wavelength-dependent. For this purpose, the fiber coupler can contain, for example, a dichroic mirror. In this way, even larger distances of several meters between the excitation laser, the spectrometer and the sample can be overcome. The excitation laser and the spectrometer then do not have to take up space in the immediate vicinity of the operating field, for example in the operating room, but can be accommodated in a place where they do not disturb. The fiber optic with the probe can be guided to the operator of the device in any way, for example from the ceiling of the operating room, in order not to create any tripping hazards.

In a further particularly advantageous embodiment of the invention, an output unit is provided which is designed to superimpose a representation of the property stored in the memory and queried with the laser beam on the overview image of the sample at the location associated with the memory. In this way, the overview image is upgraded to an “augmented reality” in a way that is immediately visible to the operator.

For example, a Raman spectrum can be evaluated in such a way that a given canon of chemical substances is then searched for. For example, a linear combination of the Raman spectra of substances from this canon can be fitted to the recorded Raman spectrum in such a way that maximum agreement results. The coefficients of the linear combination then provide a statement about the proportions in which the searched substances are present at the queried location. For example, a color can now be assigned to each substance from the canon, and these colors can, for example, be applied in the representation with intensities that are determined by the coefficients of the linear combination.

The canon of substances that are searched for can be freely selected and can be dynamically adjusted, in particular by the operator. For example, it is possible to hide certain substances for the sake of clarity.

According to the invention, a projector is provided which is designed to project a representation of the property stored in the memory and queried with the laser beam onto the sample at the location associated with the memory. This means that “augmented reality” can be further refined so that the operator no longer has to look back and forth between the sample, such as the organ, and a computer screen. For example, the operator can move the probe over an area of the organ whose chemical composition interests him and "draw" the chemical composition determined using Raman spectroscopy directly on the organ itself. The projection is particularly advantageous during longer operations, as every change in view between the organ and a computer screen requires the eyes to adjust to a different distance. These changes can become tiring over time.

In a further particularly advantageous embodiment of the invention, the imaging device comprises a bright field camera. The overview image recorded then corresponds to the normal way a person sees. In this respect, no adjustment is required if the operator moves his gaze back and forth between the sample and a computer screen with the overview image.

In a further particularly advantageous embodiment of the invention, the imaging device is designed to record a three-dimensional overview image of the sample. A three-dimensional overview image can in particular be used to control a projector so that it projects the representation of the queried property onto the sample at the correct location associated in the memory. The imaging device can in particular comprise a stereo camera and/or a strip photometry device.

For example, the local angle of incidence of the illumination on the sample, and thus the local orientation of the sample surface, can be determined using a least squares fit on overview images that are recorded under illumination from different directions. The orientation of the sample surface is then determined which leads to an intensity distribution which is least contradictory to the actually observed intensity distributions.

In a further particularly advantageous embodiment of the invention, a switching device is provided which is designed to change the intensity of the laser beam between a first, lower level for querying the properties of the sample and a second, higher level for removing material from the sample. and/or for changing the material of the sample. This switching device can be, for example, a shutter or a Pockels cell. The device can then also be used to change the property queried with the laser beam. For example, a chemical contaminant or tumor tissue can be removed.

The laser used to remove and/or modify material does not have to be the same as the laser used for interrogation. The laser intensity can also be switched by releasing the beam path from a second laser with higher intensity to the sample. For example, the laser used for interrogation can be a continuous wave laser, while the laser used for ablation and/or modification emits ultra-short pulses with very high intensity. Such pulses can interact directly with the electron shells of atoms of the material to be removed. The material can then be removed without heating the area around the sample to any significant extent.

The switching device can in particular be controlled by a manually operable trigger attached to a manually guided probe. The operator can then, for example, use the described “augmented reality” to use the probe as a “chemical eraser” in order to directly “erase” detected undesirable substances or tissue changes by sweeping over them with the probe.

In this context, it should be noted that the use of the device to support operations is an essential "use case", but is not limited to this (although corresponding methods are not part of the claimed invention). For example, a component made of a metal alloy or a plastic mixture can also be examined with a manually operated probe to determine whether the composition of the alloy or mixture is homogeneous over the entire component and whether the component therefore fulfills the promise of this composition Has practical properties through and through. Likewise, for example, a weld seam or a splice be examined to see whether the respective properties are homogeneous. For example, at the point of adhesion, areas in which the adhesive has not fully reacted into its hardened form can be identified. Sources of error here include, for example, insufficient lighting in a light-activated adhesive or insufficient mixing of the components of a multi-component adhesive.

In a further particularly advantageous embodiment of the invention, the switching device is connected to the measuring device so that it is triggered automatically when the property queried with the laser beam fulfills a predetermined condition. For example, the switching device can be activated automatically when a specific substance has been identified at the location that is queried with the laser beam. The switching device can therefore be controlled by an automatic triggering mechanism, which is triggered by the presence of a specific chemical substance. The presence of the chemical substance can be detected, for example, by Raman spectroscopy, but also, for example, by the emission of fluorescent light in response to the laser beam used for the interrogation. This allows the user to perform chemically controlled removal.

Chemically controlled removal is not only useful in the medical field. It can also be used in the cosmetic sector, for example, to selectively chemically convert or break down tattoo inks without leaving scars on the treated skin. Furthermore, graffiti paints, for example, can also be selectively removed from surfaces that are too sensitive for the use of chemical solvents.

Special description part

Figur 1:

Nicht maßstabsgerechte Schemazeichnung eines Ausführungsbeispiels der Vorrichtung 100;

Figur 2:

Beispielhafte Darstellung der "Augmented Reality" auf einer Ausgabeeinheit 71 (Figur 2a) oder direkt auf der Probe 2 (Figur 2b);

Figur 3:

Umschaltung 8 zwischen einem Anregungslaser 36 für die Abfrage der Eigenschaft 23 der Probe 2 und einem Ablationslaser 34 für den Materialabtrag von der Probe 2;

Figur 4:

Überlagerung optischer und chemischer Information am Beispiel zweier Werkstücke 91 und 92, die mit einer Klebefuge 93 verklebt sind.

The subject matter of the invention is explained below with reference to figures, without the subject matter of the invention being limited thereby. It is shown:

Figure 1:

Schematic drawing of an exemplary embodiment of the device 100, not to scale;

Figure 2:

Example representation of “Augmented Reality” on an output unit 71 ( Figure 2a ) or directly on sample 2 ( Figure 2b );

Figure 3:

Switching 8 between an excitation laser 36 for querying the property 23 of sample 2 and an ablation laser 34 for removing material from sample 2;

Figure 4:

Superimposition of optical and chemical information using the example of two workpieces 91 and 92, which are glued with an adhesive joint 93.

Figure 1 shows schematically an exemplary embodiment of the device 100. The sample 2 to be examined in this example is a liver in vivo. Other organs and body parts are omitted for clarity.

A probe 5 is guided over the sample 2 by the operator of the device 100. A glass fiber 38 is guided through the probe 5 and opens into an aperture 31. An excitation laser 36 emits a laser beam 32, which is optionally modulated in a modulator 33 with a frequency ω. The laser beam 32 reaches a fiber coupler 37 with a wavelength-dependent division ratio via a first glass fiber 37a. The laser beam 32 emerges from the aperture 31 and generates a laser spot 32a at location 23 on the sample 2. At this location 23, Raman scattered light is generated, which is characteristic of the local chemical composition of the sample 2 as the queried property 22. The Raman-scattered light, symbolized by the reference number 22 for that contained in it Information is passed through the fiber coupler 37 into a second optical fiber 37b, which leads to a Raman spectrometer 35. The distance between the aperture 31 and the sample 2 is in Figure 1 For the sake of clarity, the drawing is greatly exaggerated. The Raman spectrometer 35 determines the local chemical composition 22 of sample 2 at location 23, but itself does not yet know where this location 23 is on sample 2.

In Figure 1 Two options are shown with which the location 23 can be determined. A tracking device 4 in this regard can include at least two laser scanners 43 or radio transmitters 44, which determine the position 31a and the orientation 31b of the probe 5, and thus also of the aperture 31. The tracking device 4 can alternatively or in combination also comprise an image evaluation logic 41, 42, which contains the overview image 21 of the sample 2 supplied by a camera 1, including the laser point 32a generated therein by the laser beam 32, and from the overview image 21 the position of the laser point 32a as the Location 23 evaluated.

Each location 23 is stored in a memory 6 together with the associated queried property 22.

The aperture 31, the excitation laser 36, the modulator 33, the fiber coupler 37, the glass fibers 37, 37a and 38 connected to the fiber coupler 37 and the Raman spectrometer 35 together form the measuring instrument 3 for querying the property 22 of the sample 2.

The probe 5 contains a first trigger 51 with which the operator of the device 100 can trigger the recording of a Raman spectrum by the Raman spectrometer 35. The probe 5 also contains a second trigger 81 with which the in Figure 3 switching device 8 explained in more detail for the Material removal can be controlled. The signal connections of triggers 51 and 81 are in Figure 1 not shown for clarity.

Figure 2a shows an example of how an “augmented reality” can be displayed on an output unit 71 using the information stored in the memory 6. The output unit 71 receives the overview image 21 of the sample 2 from the camera 1 and displays it in the background. At the same time, the output unit 71 receives the values of the queried property 22 from the memory 6 together with the respective locations 23 on the sample 2. From this, the output unit 71 determines a representation 61 in which, for example, different chemical substances are displayed in different colors. The representation 61 is superimposed on the overview image 21 of sample 2.

Figure 2b shows an example of how an “augmented reality” can be created that does not require turning your gaze away from the sample 2 and towards an output unit 71. A projector 72 generates a representation 62 from the information stored in the memory 6, which is, for example, analogous to the representation 61 according to Figure 2a can be color coded. In contrast to Figure 2a the representation is projected directly onto sample 2. So every value for the queried property 22 is projected onto the associated location 23.

Figure 3 shows an example of how you can switch between querying property 22 and removing material from sample 2. The continuous laser beam 32 of the excitation laser 36 and the pulsed laser beam 34a of the ablation laser 34 are each guided into the switching device 8. The switching device 8 couples exactly one of the beams 32 and 34a into the first optical fiber 37a, which according to Figure 1 leads to the fiber coupler 37. The other beam is directed to a beam dump 82 and converted there into heat. In this way, the lasers 36 and 34 themselves do not have to be constantly switched on and off, which would be bad for their lifespan.

Figure 4 shows another application example in which normal optical contrast and chemical contrast can be combined with each other using the device 100. As sample 2, an arrangement consisting of a first workpiece 91 and a second workpiece 92, which are glued together by an adhesive joint 93, is to be examined.

Figure 4a shows those features of sample 2 that are visible in a normal optical overview image 21. The first workpiece 91 has substantially horizontal grooves 91a, and the second workpiece 92 has substantially vertical grooves 92a. The grooves 91a, 92a were created during the production of the workpieces 91 and 92. The adhesive joint 93 appears colorless and without any particular structure.

Figure 4b shows a snapshot in which sample 2 has already been partially examined with probe 5. The adhesive joint 93 is successively examined from left to right. Where the probe 5 has already been, it was identified that the adhesive joint 93 consists of properly cured adhesive 93a. This information can, for example, as in Figure 2a explained, be output on an output unit 71 or, for example, as in Figure 2b explained, can be projected directly onto sample 2.

Figure 4c shows the state in which the entire adhesive joint 93 was scanned with the probe 5. In the in Figure 4b In the area of the adhesive joint 93 that has not yet been examined, it now becomes apparent that the first component 93b and the second component 93c of the adhesive are present in separate phases and have not reacted to the final form 93a. In this area, the adhesive joint 93 is therefore faulty and cannot bear loads.

Reference symbol list

1

Device for obtaining the overview image 21

2

sample

21

Overview image of sample 2

22

Property of sample 2 queried with laser beam 32

23

Location on sample 2 where laser beam 32 queries property 22

3

Measuring instrument for local query of property 22

31

Aperture for laser beam 3

31a

Position of aperture 31

31b

Orientation of the aperture 31 in space

32

laser beam

32a

Laser spot generated by laser beam 32 on sample 2

33

Laser beam modulator 32

34

Ablation laser

34a

Ablation laser beam 34

35

Raman spectrometer

36

Excitation laser

37

fiber coupler

37a

Input of the fiber coupler 37 for laser beams 32, 34a

37b

Output of the fiber coupler 37 for the queried property 22

38

common optical fiber for laser beam 32, 34a and property 22

4

Tracking agent for location 23 on sample 2

41.42

Image evaluation logics

43

Laser scanner

44

Radio transmitter

5

probe

51

Trigger for querying property 22

6

Memory that associates property 22 to locations 23

61, 62

Representations of information in memory 6

71

Output device for overview image 21 and representation 61

72

Projector for display 62 on sample 2

8th

Switching device

81

Trigger for switching device

82

Beamdump

91

first workpiece

91a

Scoring in the first workpiece 91

92

second workpiece

92a

Scoring in the second workpiece 92

93

Adhesive joint between workpieces 91 and 92

93a

fully cured glue

93b

first component of the glue

93c

second component of the glue

100

contraption

Claims (15)

1. An apparatus (100) for examining a sample (2), comprising an imaging device (1) for obtaining an overview image (21) of the sample (2), an excitation laser (36) for providing a laser beam (32), a measuring instrument (3) for locally interrogating at least one property (22) of the sample with the laser beam (32) which emanates from an aperture (31), wherein this aperture (31) is part of a probe (5) that is manually guidable to the sample (2) by an operator of the apparatus (100), further comprising tracking means (4) for determining the location (23) on the sample (2) that is currently being interrogated with the laser beam (32), as well as a memory (6) that is configured to associate the property (22) interrogated with the laser beam (32) with the determined location (23) on the sample (2) in the memory (6), wherein the tracking means (4) are configured to determine the location (23) at which the laser beam (32) impacts the sample (2) by evaluating the so-generated laser spot (32a) from the overview image (21), and/or to determine this location (23) by measuring the position (31a) and orientation (31b) of the aperture, characterized in that a projector (72) is provided, said projector (72) being configured to project a rendering (62) of the property (22) interrogated with the laser beam (32) and stored in the memory (6) onto the sample (2) at the location (23) associated by the memory (6).
2. The apparatus (100) of claim 1, characterized in that the probe (5) comprises a manually-actuated trigger (51) for the probing of the property (22) by the measuring instrument (3).
3. The apparatus (100) of any one of claims 1 to 2, characterized in that adapting means are provided, said adapting means being configured to adapt the focus plane of the laser beam (32) emanating from the aperture (31) to a change of the distance between the aperture (31) and the sample (2).
4. The apparatus (100) of any one of claims 1 to 3, characterized in that the tracking means (4) comprise an image processing logic (41), said image processing logic (41) being configured to identify a location at which the luminance of the overview image (21) exceeds a threshold value, a center of gravity of the luminance of the overview image (21), and/or a location at which a spatial profile of the luminance of the overview image (21) matches the beam profile of the laser beam (32), as the location (23) on the sample (2) that is currently being interrogated with the laser beam (32).
5. The apparatus (100) of any one of claims 1 to 4, characterized in that a modulator (33) for intensity modulation of the laser beam (32) with a frequency ω is provided, wherein the imaging device (1) is configured for obtaining a temporal sequence of overview images (21), and wherein the tracking means (4) comprise an image processing logic (42) that is configured to determine, from the temporal sequence of overview images (21), a location at which the luminance is modulated with the frequency ω as the location (23) on the sample (2) that is currently being interrogated with the laser beam (32).
6. The apparatus (100) of any one of claims 1 to 5, characterized in that the tracking means (4) comprise at least two laser scanners (43) or radio transmitters (44) for spatial tracking of the aperture (31), respectively of the probe (5).
7. The apparatus (100) of any one of claims 1 to 6, characterized in that the measuring instrument (3) further comprises a scanning device that is configured to change the exiting angle of the laser beam (32) from the aperture (31).
8. The apparatus (100) of any one of claims 1 to 7, characterized in that the measuring instrument (3) comprises a Raman spectrometer (35) for interrogating the chemical composition of the sample (2).
9. The apparatus (100) of claim 8, characterized in that an excitation laser (36) on the one hand and the Raman spectrometer (35) on the other hand are connected to a common optical fiber (38) leading to the aperture (31) via a fiber coupler (37) whose splitting ratio is wavelength-dependent.
10. The apparatus (100) of any one of claims 1 to 9, characterized in that an output unit (71) is provided, said output unit (71) being configured to superimpose a rendering (61) of the property (22) interrogated with the laser beam (32) and stored in the memory (6) onto the overview image (21) of the sample (2) at a location (23) associated by the memory (6).
11. The apparatus (100) of any one of claims 1 to 10, characterized in that the imaging device (1) comprises a bright field camera.
12. The apparatus (100) of any one of claims 1 to 11, characterized in that the imaging device (1) is configured for recording a three-dimensional overview image (21) of the sample (2).
13. The apparatus (100) of claim 12, characterized in that the imaging device (1) comprises a stereo camera and/or a stripe photometry device.
14. The apparatus (100) of any one of claims 1 to 13, characterized in that a switching device (8) is provided, said switching device (8) being configured to switch the intensity of the laser beam (32) between a first, lower level for interrogating the property (22) of the sample (2) and a second, higher level for ablating material from the sample (2), and/or for modifying material of the sample (2).
15. The apparatus (100) of claim 14, characterized in that the switching device (8) is connected to the measuring instrument (3), such that it is triggered automatically if the property (22) interrogated with the laser beam (32) fulfils a predetermined condition.

Images